Renewable surface treatment of silicone medical devices with reactive hydrophilic polymers

ABSTRACT

The present invention is directed toward the renewable surface treatment of medical devices such as contact lenses and medical implants. In particular, the present invention is directed to a method of modifying the surface of a medical device to increase its biocompatibility or hydrophilicity by coating the device with a removable hydrophilic polymer by means of reaction between reactive functionalities on the hydrophilic polymer which functionalities are complementary to reactive functionalities on or near the surface of the medical device. The present invention is also directed to a contact lens or other medical device having such a surface coating.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related by subject matter to commonly-assigned U.S.application Ser. No. 09/315,620, filed May 20, 1999.

FIELD OF THE INVENTION

The present invention is directed toward the surface treatment ofmedical devices such as contact lenses and medical implants. Inparticular, the present invention is directed to a method of renewablymodifying the surface of a medical device to increase itsbiocompatibility or hydrophilicity by coating the device with ahydrophilic polymers by reaction between reactive functionalities in thecontact lens material and complementary reactive functionalities on thehydrophilic polymer. The present invention is also directed to a contactlens or other medical device having such a surface coating.

BACKGROUND

Contact lenses made from silicone-containing materials have beeninvestigated for a number of years. Such materials can generally besubdivided into two major classes: hydrogels and non-hydrogels.Non-hydrogels do not absorb appreciable amounts of water, whereashydrogels can absorb and retain water in an equilibrium state. Hydrogelsgenerally have a water content greater than about five weight percentand more commonly between about 10 to about 80 weight percent.Regardless of their water content, both non-hydrogel and hydrogelsilicone contact lenses tend to have relatively hydrophobic,non-wettable surfaces.

Surface structure and composition determine many of the physicalproperties and ultimate uses of solid materials. Characteristics such aswetting, friction, and adhesion or lubricity are largely influenced bysurface characteristics. The alteration of surface characteristics is ofspecial significance in biotechnical applications, wherebiocompatibility is of particular concern. Therefore, those skilled inthe art have long recognized the need for rendering the surface ofcontact lenses and other medical devices hydrophilic or morehydrophilic. Increasing the hydrophilicity of the contact-lens surfaceimproves the wettability of the contact lenses with tear fluid in theeye. This in turn improves the wear comfort of the contact lenses. Inthe case of continuous-wear lenses, the surface is especially important.The surface of a continuous-wear lens must be designed not only forcomfort, but to avoid adverse reactions such as corneal edema,inflammation, or lymphocyte infiltration. Improved methods haveaccordingly been sought for modifying the surfaces of contact lenses,particularly high-Dk (highly oxygen permeable) lenses designed forcontinuous (overnight) wear.

Various patents disclose the attachment of hydrophilic or otherwisebiocompatible polymeric chains to the surface of a contact lens in orderto render the lens more biocompatible. For example, U.S. Pat. No.5,652,014 teaches amination of a substrate followed by reaction withother polymers, such as a PEO star molecule or a sulfatedpolysaccharide. One problem with such an approach is that the polymerchain density is limited due to the difficult of attaching the polymerto the silicone substrate.

U.S. Pat. No. 5,344,701 discloses the attachment of oxazolinone orazlactone monomers to a substrate by means of plasma. The invention hasutility in the field of surface-mediated or catalyzed reactions forsynthesis or site-specific separations, including affinity separation ofbiomolecules, diagnostic supports and enzyme membrane reactors. Theoxazolinone group is attached to a porous substrate apparently byreaction of the ethylenic unsaturation in the oxazolinone monomer withradicals formed by plasma on the substrate surface. Alternatively, thesubstrate can be coated with monomers and reacted with plasma to form across-linked coating. The oxazolinone groups that have been attached tothe surface can then be used to attach a biologically active material,for example, proteins, since the oxazolinone is attacked by amines,thiols, and alcohols. U.S. Pat. No. 5,364,918 to Valint et al. and U.S.Pat. No. 5,352,714 to Lai et al. disclose the use of oxazolinonemonomers as internal wetting agents for contact lenses, which agents maymigrate to the surface of the contact lens.

U.S. Pat. No. 5,804,318 to Pinchuk et al. discloses lubrifying coatingsfor reducing the coefficients of friction of surfaces on medicaldevices, including hydrophilic copolymers containing some monomershaving pendant tertiary amine functionality. The hydrogel coatings arecovalently bondable to epoxy functionalized surfaces on the medicalequipment.

U.S. Pat. No. 4,734,475 to Goldenberg et al. discloses the use of acontact lens fabricated from a polymer comprising oxirane (epoxy)substituted monomeric units in the backbone, such that the outersurfaces of the lens contain a hydrophilic inducing amount of thereaction product of the oxirane monomeric units with a water solublereactive organic, amine, alcohol, thiol, urea, thiourea, sulfite,bisulfite or thiosulfate.

In view of the above, it would be desirable to find an optically clear,hydrophilic coating for the surface of a silicone medical device thatrenders the device more biocompatible. It would also be desirable toform a coating for a silicone hydrogel contact lens that is morecomfortable for a longer period of time, simultaneously tear-wettableand highly permeable to oxygen. It would be desirable if such abiocompatibilized lens was capable of continuous wear overnight,preferably for a week or more without adverse effects to the cornea.Further, it would be desirable to provide a coating with theseproperties that can be readily renewed to restore its properties to anas-new state.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an Atomic Force Microscopy (AFM) topographical image (50μm²) of a control contact lens described in Example 15 below, forcomparison to a contact lenses according to the invention; the image ofthe anterior side of the lens is shown on the left of FIG. 1 and theimage of the posterior side is shown on the right.

FIG. 2 shows an Atomic Force Microscopy (AFM) topographical image (50μm²) of a contact lens coated described in Example 14 according to oneembodiment of the present invention, which lens is a siliconerigid-gas-permeable lens coated with a polymer as described in Example10, a copolymer of dimethyl acrylamide and glycidyl methacrylate.

FIG. 3 shows an Atomic Force Microscopy (AFM) topographical image (50μm²) of a contact lens coated described in Example 15 according to oneembodiment of the present invention, which lens is a siliconerigid-gas-permeable lens coated with a combination of the hydrophiliccopolymers described in Examples 10 and Example 12.

FIG. 4 shows Atomic Force Microscopy (AFM) topographical image (50 μm²)of a control contact lens described in Example 16 for comparison toother lenses according to another embodiment of the present invention,which lens is a silicone hydrogel lens coated with a polymer asdescribed in Example 11.

FIG. 5 shows Atomic Force Microscopy (AFM) topographical image (50 μm²)of a contact lens coated described in Example 16 according to oneembodiment of the present invention, which lens is a silicone hydrogellens coated with a polymer as described in Example 11, a copolymer ofdimethyl acrylamide, glycidyl methacrylate, andoctafluoropentylmethacrylate.

FIG. 6 shows Atomic Force Microscopy (AFM) topographical image (50 μm²)of a contact lens coated described in Example 16 according to oneembodiment of the present invention, which lens is a silicone hydrogellens coated with a polymer as described in Example 11, a copolymer ofdimethyl acrylamide, glycidyl methacrylate, andoctafluoropentylmethacrylate, which is used for coating at a higherconcentration than was used for coating the lens in FIG. 5.

FIG. 7 is an Atomic Force Microscopy (AFM) topographical image (50 μm²)of an RGP contact lens material button of Example 18 prior to surfacetreatment.

FIG. 8 is an Atomic Force Microscopy (AFM) topographical image (50 μm²)of the surface of an RGP button after a first hydrophilic polymercoating step in Example 18.

FIG. 9 is an Atomic Force Microscopy (AFM) topographical image (50 μm²)of the surface of an RGP button after abrasive removal of the polymercoating in Example 18.

FIG. 10 is an Atomic Force Microscopy (AFM) topographical image (50 μm²)of the surface of an RGP button after the hydrophilic polymeric surfacewas reapplied in Example 18.

SUMMARY OF THE INVENTION

The present invention is directed toward surface treatment of siliconecontact lenses and other silicone medical devices, including a method ofmodifying the surface of a contact lens to increase its hydrophilicityor wettability. The surface treatment comprises the attachment ofhydrophilic polymer chains to the surface of the contact lens substrateby means of reactive functionalities in the lens substrate materialreacting with complementary reactive functionalities in monomeric unitsalong a hydrophilic reactive polymer. Subsequently the hydrophilicpolymer chains can be removed from the contact lens substrate and thenre-applied to achieve substantially as-new surface quality. As usedhere, the term “as-new surface quality” means a re-applied surfaceresembling the original surface coating in appearance and materialproperties.

The present invention is also directed to a medical device, examples ofwhich include contact lenses, intraocular lenses, catheters, implants,and the like, comprising a surface made by such a method.

Examples of medical devices that can be fabricated in accordance withthe present invention include dental appliances, including retainers andmouth guards, hearing aids, yams for clothing or for orthopaedic orother medical/surgical implants and appliances such as punctal plugs,stents and braces.

DETAILED DESCRIPTION OF THE INVENTION

As stated above, the present invention is directed toward surfacetreatment of medical devices, including contact lenses, intraocularlenses and vascular implants, to improve their biocompatibility. Thepresent invention is especially advantageous for application to contactlenses, such as hydrogels, silicone hydrogels, and rigid-gas-permeablelens materials. The invention is especially advantageous for siliconerigid-gas-permeable lenses. Both rigid-gas-permeable (“RGP”) materialsand hydrogels are well-known classes of materials. By the term silicone,it is meant that the material being treated is an organic polymercomprising at least five percent by weight silicone (—OSi—linkages),preferably 10 to 100 percent by weight silicone, more preferably 30 to90 percent by weight silicone.

RGP materials typically comprise a hydrophobic cross-linked polymersystem containing less than 5 wt. % water. RGP materials useful inaccordance with the present invention include those materials taught inU.S. Pat. No. 4,826,936 to Ellis; U.S. Pat. No. 4,463,149 to Ellis; U.S.Pat No. 4,604,479 to Ellis; U.S. Pat. No. 4,686,267 to Ellis et al.;U.S. Pat. No. 4,826,936 to Ellis; U.S. Pat. No. 4,996,275 to Ellis etal.; U.S. Pat. No. 5,032,658 to Baron et al.; U.S. Pat. No. 5,070,215 toBambury et al.; U.S. Pat. No. 5,177,165 to Valint et al.; U.S. Pat. No.5,177,168 to Baron et al.; U.S. Pat. No. 5,219,965 to Valint et al.;U.S. Pat. No.5,336,797 to McGee and Valint; U.S. Pat. No. 5,358,995 toLai et al.; U.S. Pat. No. 5,364,918 to Valint et al.; U.S. Pat. No.5,610,252 to Bambury et al.; U.S. Pat. No. 5,708,094 to Lai et al; andU.S. Pat. No. 5,981,669 to Valint et al. U.S. Pat. No. 5,346,976 toEllis et al. teaches a preferred method of making an RGP material.

Hydrogels comprise hydrated, cross-linked polymeric systems containingwater in an equilibrium state. Silicone hydrogels generally have a watercontent greater than about five weight percent and more commonly betweenabout ten to about eighty weight percent. Such materials are usuallyprepared by polymerizing a mixture containing at least onesilicone-containing monomer and at least one hydrophilic monomer. Eitherthe silicone-containing monomer or the hydrophilic monomer may functionas a cross-linking agent (a cross-linker being defined as a monomerhaving multiple polymerizable functionalities) or a separatecross-linker may be employed. Applicable silicone-containing monomericunits for use in the formation of silicone hydrogels are well known inthe art and numerous examples are provided in U.S. Pat. Nos. 4,136,250;4,153,641; 4,740,533; 5,034,461; 5,070,215; 5,260,000; 5,310,779; and5,358,995.

Examples of applicable silicon-containing monomeric units include bulkypolysiloxanylalkyl (meth)acrylic monomers. An example of bulkypolysiloxanylalkyl (meth)acrylic monomers is represented by thefollowing Formula I:

wherein:

X denotes —O— or —NR—;

each R₁₈ independently denotes hydrogen or methyl;

each R₁₉ independently denotes a lower alkyl radical, phenyl radical ora group represented by

wherein each R₁₉. independently denotes a lower alkyl or phenyl radical;and

h is 1 to 10.

Some preferred bulky monomers are methacryloxypropyltris(trimethylsiloxy)silane or tris(trimethylsiloxy)silylpropylmethacrylate, sometimes referred to as TRIS andtris(trimethylsiloxy)silylpropyl vinyl carbamate, sometimes referred toas TRIS-VC.

Such bulky monomers may be copolymerized with a silicone macromonomer,which is a poly(organosiloxane) capped with an unsaturated group at twoor more ends of the molecule. U.S. Pat. No. 4,153,641 to Deichert et al.discloses, for example, various unsaturated groups, including acryloxyor methacryloxy.

Another class of representative silicone-containing monomers includessilicone-containing vinyl carbonate or vinyl carbamate monomers such as:1,3-bis[4-vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane;3-(trimethylsilyl)propyl vinyl carbonate;3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane];3-[tris(trimethylsiloxy)silyl] propyl vinyl carbamate;3-[tris(trimethylsiloxy)silyl] propyl allyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate;t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl vinylcarbonate; and trimethylsilylmethyl vinyl carbonate.

Another class of silicon-containing monomers includespolyurethane-polysiloxane macromonomers (also sometimes referred to asprepolymers), that may have hard-soft-hard blocks like traditionalurethane elastomers. Examples of silicone urethanes are disclosed in avariety or publications, including Lai, Yu-Chin, “The Role of BulkyPolysiloxanylalkyl Methacryates in Polyurethane-Polysiloxane Hydrogels,”Journal of Applied Polymer Science, Vol. 60, 1193-1199 (1996). U.S. Pat.No. 5,760,100, 5,451,617 and 5,451,651 disclose examples of suchmonomers, which disclosures are hereby incorporated by reference intheir entirety. Further examples of silicone urethane monomers arerepresented by Formulae II and III:

(II) E(*D*A*D*G)_(a)*D*A*D*E′; or

(III) E(*D*G*D*A)_(a)*D*G*D*E′;

wherein:

D denotes an alkyl diradical, an alkyl cycloalkyl diradical, acycloalkyl diradical, an aryl diradical or an alkylaryl diradical having6 to 30 carbon atoms;

G denotes an alkyl diradical, a cycloalkyl diradical, an alkylcycloalkyl diradical, an aryl diradical or an alkylaryl diradical having1 to 40 carbon atoms and which may contain ether, thio or amine linkagesin the main chain;

* denotes a urethane or ureido linkage;

a is at least 1;

A denotes a divalent polymeric radical of Formula IV:

wherein:

each Rs independently denotes an alkyl or fluoro-substituted alkyl grouphaving 1 to 10 carbon atoms which may contain ether linkages betweencarbon atoms;

m′ is at least 1; and

p is a number that provides a moiety weight of 400 to 10,000;

each of E and E′ independently denotes a polymerizable unsaturatedorganic radical represented by Formula VI:

wherein:

R₂₃ is hydrogen or methyl;

R₂₄ is hydrogen, an alkyl radical having 1 to 6 carbon atoms, or a—CO—Y—R₂₆ radical wherein Y is —O—, —S— or —NH—;

R₂₅ is a divalent alkylene radical having 1 to 10 carbon atoms;

R₂₆ is a alkyl radical having 1 to 12 carbon atoms;

X denotes —CO— or —OCO—;

Z denotes —O— or —NH—;

Ar denotes an aromatic radical having 6 to 30 carbon atoms;

w is 0 to 6; x is 0 or 1; y is 0 or 1; and z is 0 or 1.

A preferred silicone-containing urethane monomer is represented byFormula (VII):

wherein m is at least 1 and is preferably 3 or 4, a is at least 1 andpreferably is 1, p is a number which provides a moiety weight of 400 to10,000 and is preferably at least 30, R₂₇ is a diradical of adiisocyanate after removal of the isocyanate group, such as thediradical of isophorone dilsocyanate, and each E″ is a group representedby:

Another class of representative silicone-containing monomers includesfluorinated monomers. Such monomers have been used in the formation offluorosilicone hydrogels to reduce the accumulation of deposits oncontact lenses made therefrom, as described in U.S. Pat. Nos. 4,954,587,5,079,319 and 5,010,141. The use of silicone-containing monomers havingcertain fluorinated side groups, i.e. —(CF₂)—H, have been found toimprove compatibility between the hydrophilic and silicone-containingmonomeric units, as described in U.S. Pat. Nos. 5,387,662 and 5,321,108.

In one preferred embodiment of the invention, a silicone hydrogelmaterial comprises (in bulk, that is, in the monomer mixture that iscopolymerized) 5 to 50 percent, preferably 10 to 25, by weight of one ormore silicone macromonomers, 5 to 75 percent, preferably 30 to 60percent, by weight of one or more polysiloxanylalkyl (meth)acrylicmonomers, and 10 to 50 percent, preferably 20 to 40 percent, by weightof a hydrophilic monomer. Examples of hydrophilic monomers include, butare not limited to, ethylenically unsaturated lactam-containing monomerssuch as N-vinyl pyrrolidinone, methacrylic and acrylic acids; acrylicsubstituted alcohols, such as 2-hydroxyethylmethacrylate and2-hydroxyethylacrylate and acrylamides, such as methacrylamide andN,N-dimethylacrylamide, vinyl carbonate or vinyl carbamate monomers suchas disclosed in U.S. Pat. Nos. 5,070,215, and oxazolinone monomers suchas disclosed in U.S. Pat. No. 4,910,277. Other hydrophilic monomers suchas N,N-dimethyl acrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA),glycerol methacrylate, 2-hydroxyethyl methacrylamide,polyethyleneglycol, monomethacrylate, methacrylic acid and acrylic acidare also useful in the present invention. Other suitable hydrophilicmonomers will be apparent to one skilled in the art.

The above silicone materials are merely exemplary, and other materialsfor use as substrates that can benefit by being coated according to thepresent invention have been disclosed in various publications and arebeing continuously developed for use in contact lenses and other medicaldevices.

As indicated above, the present invention is directed to themodification of the surface of a medical device such as a contact lensby means of removably attaching to the surface hydrophilic polymerchains. The term “removably attaching” refers to creating a chemicalbond between the substrate material and the hydrophilic polymer chainswhich can be severed without substantial mechanical damage to thesubstrate

The hydrophilic polymer chains of the invention can be chemically ormechanically removed from the substrate material, for example byabrasion. Suitable mechanical means include high shear fluidictreatments such as a high speed fluid jet, as well as contacting thesurface with a fluidized abrasive solid. The hydrophilic polymericsurface coating may also be mechanically removed by grinding orpolishing.

The preferred mechanical method for removing the polymeric surfacecoating of the invention from contact lenses is rubbing the contact lenswith a commercially available abrasive cleaner containing an abrasivesuch as silica or aluminum oxide together with one or more of an anionicsurfactant (such as an alkyl ether sulfonate), a nonionic surfactant(such as an ethoxylated alkyl phenol) and a cationic surfactant (such asa quaternary ammonium salt). Particularly preferred abrasive cleanersinclude Bostone® and Boston Advanced® brand abrasive cleaners,commercially available from Bausch & Lomb, Rochester, N.Y., 14604.

Suitable chemical means for removing the hydrophilic polymeric surfacecoating include oxidation, for example oxidative plasma, ozonation orcorona discharge. Other chemical means include chemical hydrolysis,hydrolytic cleavage or enzymatic removal.

The hydrophilic polymer chains are attached to the surface by means ofexposing the surface to hydrophilic reactive polymers (inclusive ofoligomers) having ring-opening or isocyanate reactive functionalitiescomplementary to reactive groups on the surface of the medical device.Alternatively, the hydrophilic polymer chains may be attached to thesurface by means of exposing the surface to hydrophilic reactivepolymers (inclusive of oligomers) having hydroxy or (primary orsecondary) amine groups complementary to azlactone reactive groups inthe silicone material or having carboxylic acid complementary groupscomplementary to epoxy reactive groups in the silicone material. Inother words, chemical functionality at the surface of the medical deviceis utilized to covalently attach hydrophilic polymers to the object orsubstrate.

The hydrophilic reactive polymers may be homopolymers or copolymerscomprising reactive monomeric units that contain either an isocyanate ora ring-opening reactive functionality optionally. Although thesereactive monomeric units may also be hydrophilic, the hydrophilicreactive polymer may also be a copolymer of reactive monomeric unitscopolymerized with one or more of various non-reactive hydrophilicmonomeric units. Lesser amounts of hydrophobic monomeric units mayoptionally be present in the hydrophilic polymer. The ring-openingmonomers include azlactone-functional, epoxy-functional andacid-anhydride-functional monomers.

Mixtures of hydrophilic reactive polymers may be employed. For example,the hydrophilic polymer chains attached to the substrate may be theresult of the reaction of a mixture of polymers comprising (a) a firsthydrophilic reactive polymer having reactive functionalities inmonomeric units along the hydrophilic polymers complementary to reactivefunctionalities on the substrate surface and, in addition, (b) a secondhydrophilic reactive polymer having supplemental reactivefunctionalities that are reactive with the first hydrophilic reactivepolymer. A mixture comprising an epoxy-functional polymer with anacid-functional polymer, either simultaneously or sequentially appliedto the substrate to be coated, have been found to provide relativelythick coatings. Utilizing a mixture of reactive polymers provides ameans to further adjust the surface chemistry of a substrate material.

Preferably the hydrophilic reactive polymers comprise 1 to 100 molepercent of reactive monomeric units, more preferably 5 to 50 molepercent, most preferably 10 to 40 mole percent. The polymers maycomprise 0 to 99 mole percent of non-reactive hydrophilic monomericunits, preferably 50 to 95 mole percent, more preferably 60 to 90 molepercent (the reactive monomers, once reacted may also be hydrophilic,but are by definition mutually exclusive with the monomers referred toas hydrophilic monomers which are non-reactive). The weight averagemolecular weight of the hydrophilic reactive polymer may suitably rangefrom about 200 to 1,000,000, preferably from about 1,000 to 500,000,most preferably from about 5,000 to 100,000.

Hydrophilic monomers may be aprotic types such as acrylamides(N,N-dimethylacrylamide, DMA), lactams such as N-vinylpyrrolidinone, andpoly(alkylene oxides) such as methoxypolyoxyethylene methacrylates ormay be protic types such as methacrylic acid or hydroxyalkyl(meth)acrylates such as hydroxyethyl (meth)acrylate. Hydrophilicmonomers may also include anionic surfactants such as sodiumacrylamido-2-methylpropylsulfonate (AMPS) and zwitterions such asN,N-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl)-ammonium betain (SPE)and N,N-dimethyl-N-methacrylamidopropyl-N-(3-sulfopropyl)-ammoniumbetain (SPP).

Monomeric units which are hydrophobic optionally may be used in amountsup to 35 mole percent, preferably 0 to 20 mole percent, most preferably0 to 10 mole percent. Examples of hydrophobic monomers are alkylmethacrylate, fluorinated alkyl methacrylates, long-chain acrylamidessuch as octyl acrylamide, and the like.

As mentioned above, the hydrophilic reactive polymer may comprisereactive monomeric units derived from azlactone-functional,epoxy-functional and acid-anhydride-functional monomers. For example, anepoxy-functional hydrophilic reactive polymer for coating a lens can bea copolymer containing glycidyl methacrylate (GMA) monomeric units,which will react, for example, with a lens substrate comprisingcarboxylic acid groups. Preferred examples of anhydride-functionalhydrophilic reactive polymers comprise monomeric units derived frommonomers such as maleic anhydride and itaconic anhydride.

In general, epoxy-functional reactive groups or anhydride-functionalreactive groups in the hydrophilic reactive polymer react withcarboxylic (—COOH), alcohol (—OH), primary amine (—NH₂) groups or thiolgroups (—SH) in the substrate, for example, substrates made frompolymers comprising as monomeric units from methacrylic acid (MAA),hydroxyalkylmethacrylates such as hydroxyethylmethacrylate (HEMA), oraminoalkyl methacrylates such as aminopropylmethacrylate, all common andcommercially available monomers. In the case of alcohols, a catalystsuch as 4-dimethylaminopyridine may be used to speed the reaction atroom temperature, as will be understood by the skilled chemist. Acidicgroups may also be created in the substrate by the use of azlactonemonomeric units that are hydrolyzed to the acid. These acid groups canbe reacted with an epoxy or anhydride group in the hydrophilic reactivepolymer. See, for example, U.S. Pat. No. 5,364,918 to Valint et al.,herein incorporated by reference in its entirety, for examples of suchsubstrates.

In general, azlactone or isocyanate-functional groups in the hydrophilicreactive polymers may similarly react with amines or alcohols in thepolymer substrate, reactions involving an alcohol preferably in thepresence of a catalyst. In addition, carboxylic acids, amines andhydrolyzed azlactones in the hydrophilic reactive polymers may reactwith epoxy-groups in the substrate, for example, the monomeric unitsdescribed in U.S. Pat. No. 4,734,475 to Goldenberg et al., hereinincorporated by reference in its entirety.

In a preferred embodiment of the invention, preformed(non-polymerizable) hydrophilic polymers containing repeat units derivedfrom at least one ring-opening monomer, an isocyanate-containingmonomer, an amine-containing monomer, a hydroxy-containing monomer, or acarboxylic containing monomer are reacted with reactive groups on thesurface of the medical device such as a contact lens substrate.Typically, the hydrophilic reactive polymers are attached to thesubstrate at one or more places along the chain of the polymer. Afterattachment, any unreacted reactive functionalities in the hydrophilicreactive polymer may be hydrolyzed to a non-reactive moiety, in the caseof epoxy, isocyanate or ring-opening monomeric units.

Suitable hydrophilic non-reactive monomers for comprising thehydrophilic reactive polymers include generally water solubleconventional vinyl monomers such as 2-hydroxyethyl-; 2- and3-hydroxypropyl-; 2,3-dihydroxypropyl-; polyethoxyethyl-; andpolyethoxypropylacrylates, methacrylates, acrylamides andmethacrylamides; acrylamide, methacrylamide, N-methylacrylamide,N-methylmethacrylamide, N,N-dimethylacrylamide,N,N-dimethylmethacrylamide, N,N-dimethyl- and N,N-diethyl-aminoethylacrylate and methacrylate and the corresponding acrylamides andmethacrylamides; 2- and 4-vinylpyridine; 4- and2-methyl-5-vinylpyridine; N-methyl-4-vinylpiperidine;2-methyl-1-vinylimidazole; N,-N-dimethylallylamine; dimethylaminoethylvinyl ether and N-vinylpyrrolidone.

Included among the useful non-reactive monomers are generally watersoluble conventional vinyl monomers such as acrylates and methacrylatesof the general structure

where R₂ is hydrogen or methyl and R₃ is hydrogen or is an aliphatichydrocarbon group of up to 10 carbon atoms substituted by one or morewater solubilizing groups such as carboxy, hydroxy, amino, loweralkylamino, lower dialkyamino, a polyethylene oxide group with from 2 toabout 100 repeating units, or substituted by one or more sulfate,phosphate, sulfonate, phosphonate, carboxamido, sulfonamido orphosphonamido groups, or mixtures thereof;

Preferably R₃ is an oligomer or polymer such as polyethylene glycol,polypropylene glycol, poly(ethylene-propylene) glycol, poly(hydroxyethylmethacrylate), poly(dimethyl acrylamide), poly(acrylic acid),poly(methacrylic acid), polysulfone, poly(vinyl alcohol),polyacrylamide, poly(acrylamide-acrylic acid) poly(styrene sulfonate)sodium salt, poly(ethylene oxide), poly(ethylene oxide-propylene oxide),poly(glycolic acid), poly(lactic acid), poly(vinylpyrrolidone),cellulosics, polysaccharides, mixtures thereof, and copolymers thereof;

acrylamides and methacrylamides of the formula:

where R₂ and R₃ are as defined above;

acrylamides and methacrylamides of the formula:

where R₄ is lower alkyl of 1 to 3 carbon atoms and R₂ is as definedabove;

itaconates of the formula:

where R₃ is as defined above;

maleates and fumarates of the formula:

R₃OOCH═CHCOOR₃

wherein R₃ is as defined above;

vinyl ethers of the formula

 H₂C═CH—O—R₃

where R₃ is as defined above;

aliphatic vinyl compounds of the formula

R₂CH═CHR₃

where R₂ is as defined above and R₃ is as defined above with the provisothat R₃ is other than hydrogen; and

vinyl substituted heterocycles, such as vinyl pyridines, piperidines andimidazoles and N-vinyl lactams, such as N-vinyl-2-pyrrolidone.

Included among the useful water soluble monomers are acrylic andmethacrylic acid; itaconic, crotonic, fumaric and maleic acids and thelower hydroxyalkyl mono and diesters thereof, such as the 2-hydroxethylfumarate and maleate, sodium acrylate and methacrylate;2-methacryloyloxyethylsulfonic acid and allylsulfonic acid.

The inclusion of some hydrophobic monomers in the hydrophilic reactivepolymers may provide the benefit of causing the formation of tinydispersed polymer aggregates in solution, evidenced by a haziness in thesolution of the polymer. Such aggregates can also be observed in AtomicForce Microscopy images of the coated medical device.

Suitable hydrophobic copolymerizable monomers include water insolubleconventional vinyl monomers such as acrylates and methacrylates of thegeneral formnula:

where R₂ is as defined above and R₅ is a straight chain or branchedaliphatic, cycloaliphatic or aromatic group having up to 20 carbon atomswhich is unsubstituted or substituted by one or more alkoxy, alkanoyloxyor alkyl of up to 12 carbon atoms, or by halo, especially chloro orpreferably fluoro, C2 to C5 polyalkyleneoxy of 2 to about 100 units oran oligomer such as polyethylene, poly(methyl methacrylate), poly(ethylmethacrylate), or poly(glycidyl methacrylate), mixtures thereof, andcopolymers thereof;

acrylamides and methacylamides of the general formula:

where R₂ and R₅ are defined above;

vinyl ethers of the formula

H₂C═CH—O—R₅

where R₅ is as defined above;

vinyl esters of the formula

H₂C═CH—OCO—R₅

where R₅ is as defined above;

itaconates of the formula:

where R₅ is as defined above;

maleates and fumarates of the formula

R₅OOC—HC═CH—OOOR₅

where R₅ is as defined above; and

vinylic substituted hydrocarbons of the formula:

R₂CH═CHR₅

where R₂ and R₅ is as defined above

Useful or suitable hydrophobic monomers include, for example: methyl,ethyl, propyl, isopropyl, butyl, ethoxyethyl, methoxyethyl,ethoxypropyl, phenyl, benzyl, cyclohexyl, hexafluoroisopropyl, orn-octyl-acrylates and—methacrylates as well as the correspondingacrylamides and methacrylamides; dimethyl fumarate, dimethyl itaconate,dimethyl maleate, diethyl fumarate, methyl vinyl ether, ethoxyethylvinyl ether, vinyl acetate, vinyl propionate, vinyl benzoate,acrylonitrile, styrene, alpha-methylstyrene, 1-hexene, vinyl chloride,vinyl methylketone, vinyl stearate, 2-hexene and 2-ethylhexylmethacrylate.

The hydrophilic reactive polymers are synthesized in a manner known perse from the corresponding monomers (the term monomer here also includinga macromer) by a polymerization reaction customary to the person skilledin the art. Typically, the hydrophilic reactive polymers or chains areformed by: (1) mixing the monomers together; (2) adding a polymerizationinitiator; (3) subjecting the monomer/initiator mixture to a source ofultraviolet or actinic radiation and/or elevated temperature and curingsaid mixture. Typical polymerization initiators includefree-radical-generating polymerization initiators of the typeillustrated by acetyl peroxide, lauroyl peroxide, decanoyl peroxide,coprylyl peroxide, benzoyl peroxide, tertiary butyl peroxypivalate,sodium percarbonate, tertiary butyl peroctoate, andazobis-isobutyronitrile (AIBN). Ultraviolet free-radical initiatorsillustrated by diethoxyacetophenone can also be used. The curing processwill of course depend upon the initiator used and the physicalcharacteristics of the comonomer mixture such as viscosity. In anyevent, the level of initiator employed will vary within the range of0.001 to 2 weight percent of the mixture of monomers. Usually, a mixtureof the above-mentioned monomers is warmed with addition of afree-radical former.

A polymerization to form the hydrophilic reactive polymer can be carriedout in the presence or absence of a solvent. Suitable solvents are inprinciple all solvents which dissolve the monomer used, for examplewater; alcohols such as lower alkanols, for example, ethanol andmethanol; carboxamides such as dimethylformamide, dipolar aproticsolvents such as dimethyl sulfoxide or methyl ethyl ketone; ketones suchas acetone or cyclohexanone; hydrocarbons such as toluene; ethers suchas THF, dimethoxyethane or dioxane; halogenated hydrocarbons such astrichloroethane, and also mixtures of suitable solvents, for examplemixtures of water and an alcohol, for example a water/ethanol orwater/methanol mixture.

In a method according to the present invention, the contact lens orother medical device may be exposed to hydrophilic reactive polymers byimmersing the substrate in a solution containing the polymers. Forexample, a contact lens may be placed or dipped for a suitable period oftime in a solution of the hydrophilic reactive polymer or copolymer in asuitable medium, for example, an aprotic solvent such as acetonitrile.

As indicated above, one embodiment of the invention involves theattachment of reactive hydrophilic polymers to a medical device, whichpolymers comprise isocyanate-containing monomeric units or ring-openingmonomeric units. In one embodiment of the present invention, thering-opening reactive monomer has an azlactone group represented by thefollowing formula:

wherein R³ and R⁴ independently can be an alkyl group having 1 to 14carbon atoms, a cycloalkyl group having 3 to 14 carbon atoms, an arylgroup having 5 to 12 ring atoms, an arenyl group having 6 to 26 carbonatoms, and 0 to 3 heteroatoms non-peroxidic selected from S, N, and O,or R³ and R⁴ taken together with the carbon to which they are joined canform a carbocyclic ring containing 4 to 12 ring atoms, and n is aninteger 0 or 1. Such monomeric units are disclosed in U.S. Pat. No.5,177,165 to Valint et al.

The ring structure of such reactive functionalities is susceptible tonucleophilic ring-opening reactions with complementary reactivefunctional groups on the surface of the substrate being treated. Forexample, the azlactone functionality can react with primary amines,hydroxyls, or thiols in the substrate, as mentioned above, to form acovalent bond between the substrate and the hydrophilic reactive polymerat one or more locations along the polymer. A plurality of attachmentscan form a series of polymer loops on the substrate, wherein each loopcomprises a hydrophilic chain attached at both ends to the substrate.

Azlactone-functional monomers for making the hydrophilic reactivepolymer can be any monomer, prepolymer, or oligomer comprising anazlactone functionality of the above formula in combination with avinylic group on an unsaturated hydrocarbon to which the azlactone isattached. Preferably, azlactone-functionality is provided in thehydrophilic polymer by 2-alkenyl azlactone monomers. The 2-alkenylazlactone monomers are known compounds, their synthesis being described,for example, in U.S. Pat. Nos. 4,304,705; 5,081,197; and 5,091,489 (allHeilmann et al.) the disclosures of which are incorporated herein byreference. Suitable 2-alkenyl azlactones include:

2-ethenyl-1,3-oxazolin-5-one,

2-ethenyl-4-methyl-1,3-oxazolin-5-one,

2-isopropenyl-1,3-oxazolin-5-one,

2-isopropenyl-4-methyl-1,3-oxazolin-5-one,

2-ethenyl-4,4-dimethyl-1,3-oxazolin-5-one,

2-isopropenyl-4,-dimethyl-1,3-oxazolin-5-one,

2-ethenyl-4-methyl-ethyl-1,3-oxazolin-5-one,

2-isopropenyl-4-methyl-4-butyl-1,3-oxazolin-5-one,

2-ethenyl-4,4-dibutyl-1,3-oxazolin-5-one,

2-isopropenyl-4-methyl-4-dodecyl-1,3-oxazolin-5-one,

2-isopropenyl-4,4-diphenyl-1,3-oxazolin-5-one,

2-isopropenyl-4,4-pentamethylene-1,3-oxazolin-5-one,

2-isopropenyl-4,4-tetramethylene-1,3-oxazolin-5-one,

2-ethenyl-4,4-diethyl-1,3-oxazolin-5-one,

2-ethenyl-4-methyl-4-nonyl-1,3-oxazolin-5-one,

2-isopropenyl-methyl-4-phenyl-1,3-oxazolin-5-one,

2-isopropenyl-4-methyl-4-benzyl-1,3-oxazolin-5-one, and

2-ethenyl-4,4-pentamethylene-1,3-oxazolin-5-one,

More preferably, the azlactone monomers are a compound represented bythe

following general formula:

where R¹ and R² independently denote a hydrogen atom or a lower alkylradical with one to six carbon atoms, and R³ and R⁴ independently denotealkyl radicals with one to six carbon atoms or a cycloalkyl radical withfive or six carbon atoms. Specific examples include2-isopropenyl-4,4-dimethyl-2-oxazolin-5-one (IPDMO),2-vinyl-4,4-dimethyl-2-oxazolin-5-one (VDMO),spiro-4′-(2′-isopropenyl-2′-oxazolin-5-one) cyclohexane (IPCO),cyclohexane-spiro-4′-(2′-vinyl-2′-oxazol-5′-one) (VCO), and2-(-1-propenyl)-4,4-dimethyl-oxazol-5-one (PDMO) and the like.

These compounds may be prepared by the general reaction sequence:

The first step is a Shotten-Bauman acylation of an amino acid. Thepolymerizable functionality is introduced by using either acryloyl ormethacryloyl chloride. The second step involves a ring closure with achloroformate to yield the desired oxazolinone. The product is isolatedand purified by the usual procedures of organic chemistry.

As indicated above, the compounds can be copolymerized with hydrophilicand/or hydrophobic comonomers to form hydrophilic reactive polymers.After attachment to the desired substrate, any unreacted oxazolinonegroups may then be hydrolyzed in order to convert the oxazolinonecomponents into amino acids. In general, the hydrolysis step will followthe general reaction of:

The carbon-carbon double bond between the R¹ and R² radicals is shownunreacted, but the reaction can take place when copolymerized into apolymer.

Non-limiting examples of comonomers useful to be copolymerized withazlactone functional moieties to form the hydrophilic reactive polymersused to coat a medical device include those mentioned above, preferablydimethylacrylamide, N-vinyl pyrrolidinone. Further examples ofcomonomers are disclosed in European Pat. Publication 0 392 735, thedisclosure of which is incorporated by reference. Preferably,dimethylacrylamide is used as a comonomer in order to imparthydrophilicity to the copolymer.

Such azlactone-functional monomers can be copolymerized with othermonomers in various combinations of weight percentages. Using a monomerof similar reactivity ratio to that of an azlactone monomer will resultin a random copolymer. Determnination of reactivity ratios forcopolymerization are disclosed in Odian, Principles of Polymerization,2nd Ed., John Wiley & Sons, p. 425-430 (1981), the disclosure of whichis incorporated by reference herein. Alternatively, use of a comonomerhaving a higher reactivity to that of an azlactone will tend to resultin a block copolymer chain with a higher concentration ofazlactone-functionality near the terminus of the chain.

Although not as preferred as monomers, azlactone-functional prepolymersor oligomers having at least one free-radically polymerizable site canalso be utilized for providing azlactone-functionality in thehydrophilic reactive polymer according to the present invention.Azlactone-functional oligomers, for example, are prepared by freeradical polymerization of azlactone monomers, optionally with comonomersas described in U.S. Pat. Nos. 4,378,411 and 4,695,608, incorporated byreference herein. Non-limiting examples of azlactone-functionaloligomers and prepolymers are disclosed in U.S. Pat. Nos. 4,485,236,5,081,197 and 5,292,840, all incorporated by reference herein.

In another embodiment of the invention, the ring-opening reactive groupin the hydrophilic reactive polymer is an epoxy functionality. Thepreferred epoxy-functional monomer is an oxirane-containing monomer suchas glycidyl methacrylate, allyl glycidyl ether,4-vinyl-1-cyclohexene-1,2-epoxide and the like, although otherepoxy-containing monomers may be used.

The hydrophilic reactive polymers are attached to medical devices whichmay be made by conventional manufacturing processes. For example,contact lenses for application of the present invention can bemanufactured employing various conventional techniques, to yield ashaped article having the desired posterior and anterior lens surfaces.Spincasting methods are disclosed in U.S. Pat. Nos. 3,408,429 and3,660,545; preferred static casting methods are disclosed in U.S. Pat.Nos. 4,113,224 and 4,197,266. Curing of the monomeric mixture is oftenfollowed by a machining operation in order to provide a contact lenshaving a desired final configuration. As an example, U.S. Pat. No.4,555,732 discloses a process in which an excess of a monomeric mixtureis cured by spincasting in a mold to form a shaped article having ananterior lens surface and a relatively large thickness. The posteriorsurface of the cured spincast article is subsequently lathe cut toprovide a contact lens having the desired thickness and posterior lenssurface. Further machining operations may follow the lathe cutting ofthe lens surface, for example, edge-finishing operations.

After producing a lens having the desired final shape, it is desirableto remove residual solvent from the lens before edge-finishingoperations. This is because, typically, an organic diluent is includedin the initial monomeric mixture in order to minimize phase separationof polymerized products produced by polymerization of the monomericmixture and to lower the glass transition temperature of the reactingpolymeric mixture, which allows for a more efficient curing process andultimately results in a more uniformly polymerized product. Sufficientuniformity of the initial monomeric mixture and the polymerized productare of particular concern for silicone hydrogels, primarily due to theinclusion of silicone-containing monomers which may tend to separatefrom the hydrophilic comonomer. Suitable organic diluents include, forexample, 2-hydoxy, 2-methyl decane, monohydric alcohols, with C₆-C₁₀straight-chained or branched alcohols including aliphatic monohydricalcohols such as n-hexanol and n-nonanol being especially preferred.U.S. Pat. No. 6,020,445 to Vanderlaan et al. discloses suitable alcoholsand is incorporated herein by reference. Other useful solvents includediols such as ethylene glycol; polyols such as glycerin; ethers such asdiethylene glycol monoethyl ether; ketones such as methyl ethyl ketone;esters such as methyl enanthate; and hydrocarbons such as toluene.Preferably, the organic diluent is sufficiently volatile to facilitateits removal from a cured article by evaporation at or near ambientpressure. Generally, the diluent is included at five to sixty percent byweight of the monomeric mixture, with ten to fifty percent by weightbeing especially preferred.

The cured lens is then subjected to solvent removal, which can beaccomplished by evaporation at or near ambient pressure or under vacuum.An elevated temperature can be employed to shorten the time necessary toevaporate the diluent. The time, temperature and pressure conditions forthe solvent removal step will vary depending on such factors as thevolatility of the diluent and the specific monomeric components, as canbe readily determined by one skilled in the art. According to apreferred embodiment, the temperature employed in the removal step ispreferably at least 50° C., for example, 60 to 80° C. A series ofheating cycles in a linear oven under inert gas or vacuum may be used tooptimize the efficiency of the solvent removal. The cured article afterthe diluent removal step should contain no more than twenty percent byweight of diluent, preferably no more than five percent by weight orless.

Following removal of the organic diluent, the lens is next subjected tomold release and optional machining operations. The machining stepincludes, for example, buffing or polishing a lens edge and/or surface.Generally, such machining processes may be performed before or after thearticle is released from a mold part. Preferably, the lens is dryreleased from the mold by employing vacuum tweezers to lift the lensfrom the mold, after which the lens is transferred by means ofmechanical tweezers to a second set of vacuum tweezers and placedagainst a rotating surface to smooth the surface or edges. The lens maythen be turned over in order to machine the other side of the lens.

Subsequent to the mold release/machining operations, the lens issubjected to surface treatment according to the present invention, asdescribed above, including the attachment of the hydrophilic reactivepolymer chains.

Subsequent to the step of surface treatment, the lens may be subjectedto extraction to remove residuals in the lenses. Generally, in themanufacture of contact lenses, some of the monomer mix is not fullypolymerized. The incompletely polymerized material from thepolymerization process may affect optical clarity or may be harmful tothe eye. Residual material may include solvents not entirely removed bythe previous solvent removal operation, unreacted monomers from themonomeric mixture, oligomers present as by-products from thepolymerization process, or even additives that may have migrated fromthe mold used to form the lens.

Conventional methods to extract such residual materials from thepolymerized contact lens material include extraction with an alcoholsolution for several hours (for extraction of hydrophobic residualmaterial) followed by extraction with water (for extraction ofhydrophilic residual material). Thus, some of the alcohol extractionsolution remains in the polymeric network of the polymerized contactlens material, and should be extracted from the lens material before thelens may be worn safely and comfortably on the eye. Extraction of thealcohol from the lens can be achieved by employing heated water forseveral hours. Extraction should be as complete as possible, sinceincomplete extraction of residual material from lenses may contributeadversely to the useful life of the lens. Also, such residuals mayimpact lens performance and comfort by interfering with optical clarityor the desired uniform hydrophilicity of the lens surface. It isimportant that the selected extraction solution in no way adverselyaffects the optical clarity of the lens. Optical clarity is subjectivelyunderstood to be the level of clarity observed when the lens is visuallyinspected.

Subsequent to extraction, the lens is subjected to hydration in whichthe lens is fully hydrated with water, buffered saline, or the like.When the lens is ultimately fully hydrated (wherein the lens typicallymay expand by 10 to about 20 percent or more), the coating remainsintact and bound to the lens, providing a durable, hydrophilic coatingwhich has been found to be resistant to delamination.

Following hydration, the lens may undergo cosmetic inspection whereintrained inspectors inspect the contact lenses for clarity and theabsence of defects such as holes, particles, bubbles, nicks, tears.Inspection is preferably at 10×magnification. After the lens has passedthe steps of cosmetic inspection, the lens is ready for packaging,whether in a vial, plastic blister package, or other container formaintaining the lens in a sterile condition for the consumer. Finally,the packaged lens is subjected to sterilization, which sterilization maybe accomplished in a conventional autoclave, preferably under an airpressurization sterilization cycle, sometime referred to as an air-steammixture cycle, as will be appreciated by the skilled artisan. Preferablythe autoclaving is at 100° C. to 200° C. for a period of 10 to 120minutes. Following sterilization, the lens dimension of the sterilizedlenses may be checked prior to storage.

Examples of rigid-gas-permeable (“RGP”) materials useful in the presentinvention include the materials prepared from silicone-containingmonomers as taught in U.S. Pat. Nos. 4,152,508; 4,330,383; 4,686,267;4,826,889; 4,826,936; 4,861,850; 4,996,275; and 5,346,976. The teachingsof these patents are expressly incorporated herein by reference. The RGPmaterials do not generally require solvent removal or extraction stepsbefore they are used as substrates in accordance with the invention.

Objects and advantages of this invention are further illustrated by thefollowing examples, but the particular materials and amounts thereofrecited in these examples, as well as other conditions and detailsshould not be construed at unduly limit this invention.

EXAMPLE 1

This example discloses a representative silicone hydrogel lens materialused as a coating substrate in the following Examples. The formulationfor the material is provided in Table 1 below.

TABLE 1 Component Parts by Weight TRIS-VC 55 NVP 30 V₂D₂₅ 15 VINAL 1n-nonanol 15 Darocur 0.2 tint agent 0.05

The following materials are designated above:

TRIS-VC tris(trimethylsiloxy)silylpropyl vinyl carbamate NVP N-vinylpyrrolidone V₂D₂₅ a silicone-containing vinyl carbonate as previouslydescribed in U.S. Pat. No. 5,534,604. VINAL N-vinyloxycarbonyl alanineDarocur Darocur-1173, a UV initiator tint agent1,4-bis[4-(2-methacryloxyethyl)phenylamino] anthraquinone

EXAMPLE 2

This Example illustrates a process for preparation of a contact lensprior to surface modification of a contact lens according to the presentinvention. Silicone hydrogel lenses made of the formulation of Example 1above were cast-molded from polypropylene molds. Under an inert nitrogenatmosphere, 45-μl of the formulation was injected onto a cleanpolypropylene concave mold half and covered with the complementarypolypropylene convex mold half. The mold halves were compressed at apressure of 70 psi and the mixture was cured for about 15 minutes in thepresence of UV light (6-11 mW/cm² as measured by a Spectronic UV meter).The mold was exposed to UV light for about 5 additional minutes. The topmold half was removed, and the lenses were maintained at 60° C. for 3hours in a forced air oven to remove n-nonanol. Subsequently, the lensedges were ball buffed for 10 seconds at 2300 rpm with a force of 60 g.

EXAMPLE 3

This example illustrates the synthesis of the hydrophilic reactivecopolymer involving a 80/20 by weight percent ratio of monomers(DMA/VDMO) employing the ingredients in Table 2 below:

TABLE 2 Reagents Amount (g) Amount (m) Dimethylacrylamide (DMA) 16 g0.1614 Vinyl-4,4-dimethyl-2-oxazolin-5-one 4 g 0.0288 (VDMO) VAZO-64initiator 0.031 g 0.1 percent Toluene 200 ml —

All ingredients except VAZO-64 were placed in a 500-ml round-bottomflask equipped with a magnetic stirrer, condenser, argon blanket, andthermo-controller. The above was de-aerated with argon for 30 min. AfterVAZO-64 was added, the solution was heated to 60° C. and maintained for50 hrs. After the reaction was complete as monitored by FTIR (FourierTransform Infrared spectroscopy), the solution was slowly added to 2500ml of diethyl ether to precipitate the polymer. The mixture was stirred10 min, allowed to settle 10 min, and filtered. The precipitate wasdried under vacuum at 30 to 35° C. overnight, and the molecular weightdetermined to be Mn=19448, Mw=43548 and Pd=2.25, all based onpolystyrene standards. (Pd refers to polydispersity.)

EXAMPLE 4

This Example illustrates the synthesis of a prepolymer ofN,N-dimethylacrylamide that is used in making a macromonomer (or“acromer”) for eventual use in a reactive hydrophilic polymer accordingto the present invention. The prepolymer is made according to thefollowing reaction scheme.

Reagents DMA (200 g, 2.0 moles), mercaptoethanol (3.2 g, 0.041 moles),AIBN (Vazo-64 in the amount 3.3 g, 0.02 moles) and tetrahydrofuran(1,000 ml) were combined in a two liter round bottom flask fitted with amagnetic stirrer, condenser, thermal controller and a nitrogen inlet.Nitrogen gas was bubbled through the solution for one half-hour. Thetemperature was increased to 60° C. for 72 hours under a passive blanketof nitrogen. The polymer was precipitated from the reaction mixture with20 liters of ethyl ether (171.4 g of polymer was isolated). A samplesubmitted for SEC (size exclusion chromatography) analysis gave aMn=3711, Mw=7493, and Pd=2.02.

EXAMPLE 5

This Example illustrates the synthesis of a macromer of DMA using theprepolymer of Example 4 which macromonomer is used to make thehydrophilic reactive polymer of Examples 6 and 8 below, whichmacromonomer is made according to the following reaction scheme:

The prepolymer from Example 4 (150 g, 0.03 moles),isocyanatoethylmethacrylate (IEM, 5.6 g, 0.036 moles),dibutyltindilaurate (0.23 g, 3.6×10⁻⁵ moles), tetrahydrofuran (THF, 1000ml) and 2,6-di-tert-butyl-4-methyl phenol (BHT, 0.002 g, 9×10⁻⁶ moles)were combined under a nitrogen blanket. The mixture was heated to 35° C.with good stirring for seven hours. Heating was stopped, and the mixturewas allowed to stir under nitrogen overnight. Several ml of methanolwere added to react with any remaining IEM. The macromonomer was thencollected after precipitation from a large volume (16 liters) of ethylether. The solid was dried under house vacuum (yield 115 g). Sizeexclusion chromatography of the polymer verses polystyrene standardsgave the following results: Mn=2249, Mw=2994, and Pd=1.33.

EXAMPLE 6

This Example illustrates the preparation of a DMA/DMA-mac/VDMO polymerwhich may be used to form a coating according to the present invention.Dimethylacrylamide (DMA) in the amount of 16 g (0.1614 mole),vinyl-4,4-dimethyl-2-oxazolin-5-one (VDMO) in the amount of 2 g (0.0144mole), dimethylacrylamide macromer (DMA-mac) as prepared in Example 5,in the amount of 2 g (0.0004 mole), and 200 ml of toluene were placed ina 500-ml round-bottom flask equipped with a magnetic stirrer, condenser,argon blanket, and temperature controller. The solution was de-aeratedwith argon for 30 min. Then 0.029 g (0.1 mole %) of VAZO-64 was addedand the reaction heated to 60° C. for 50 hrs. After the reaction wascomplete (monitored by FTIR), the solution was slowly added to 2500 mlof ethyl ether to precipitate the polymer. After the addition wascomplete, the mixture was stirred 10 min, allowed to settle 10 min, andfiltered. The precipitate was dried under house vacuum at 30 to 35° C.overnight. The dried polymer was sampled for analysis by gel permeationchromatography, bottled and stored in a desiccator.

EXAMPLE 7

This Example illustrates the preparation of a DMA/PEOMA/VDMO polymerusable to coat a silicone substrate according to the present invention.Dimethylacrylamide, in the amount of 12 g (0.1211 mole),vinyl-4,4-dimethyl-2-oxazolin-5-one in the amount of 4 g (0.0288 mole),and 4 g (0.0036 mole) PEO methacrylate (PEOMA), which monomer has a MWof 1000, and 200 ml of toluene were placed in a 500 ml round-bottomflask equipped with a magnetic stirrer, condenser, argon blanket, andtemperature controller. The solution was de-aerated with argon for 30min. Then 0.025 g (0.1 mole %) of VAZO-64 was added, and the reactionheated to 60° C. for 50 hrs. After the reaction was complete (monitoredby FTIR), the solution was slowly added to 2500 ml of ethyl ether to thepolymer. After the addition was complete, the mixture was stirred 10min, allowed to settle 10 min, and filtered. The precipitate was driedunder house vacuum at 30 to 35° C. overnight. The dried polymer wassampled for analysis by gel permeation chromatography, bottled andstored in a desiccator.

EXAMPLE 8

This Example illustrates the synthesis of a hydrophilic reactive polymerhaving a brush or branched structure with DMA chains pendent from thebackbone of the polymer. The polymer consisted of the combination of theDMA macromonomer, glycidyl methacrylate, and DMA monomer, prepared asfollows. To a reaction flask were added distilled N,N-dimethylacrylamide(DMA, 32 g, 0.32 moles), DMA macromer from Example 5 in the amount of 4g (0.0008 moles), distilled glycidyl methacrylate (GM, 4.1 g, 0.029moles), Vazo-64 (AIBN, 0.06 g, 0.00037 moles) and toluene (500 ml). Thereaction vessel was fitted with a magnetic stirrer, condenser, thermalcontroller, and a nitrogen inlet. Nitrogen was bubbled through thesolution for 15 min to remove any dissolved oxygen. The reaction flaskwas then heated to 60° C. under a passive blanket of nitrogen for 20hours. The reaction mixture was then added slowly to 4 liters of ethylether with good mechanical stirring. The reactive polymer precipitatedand was collected by vacuum filtration. The solid was placed in a vacuumoven at 30° C. overnight to remove the ether, leaving 33.2 g of reactivepolymer (83% yield). The reactive polymer was placed in a desiccator forstorage until use.

EXAMPLE 9

This example illustrates the synthesis of avinylpyrrrolidone-co-4-vinylcyclohexyl-1,2-epoxide polymer (NVP-co-VCH)useful to coat a silicone substrate according to the present invention.The polymer was prepared based on the following reaction scheme:

To a 1 liter reaction flask were added distilled N-vinylpyrrolidone(NVP, 53.79 g, 0.48 moles), 4-vinylcyclohexyl-1,2-epoxide (VCHE, 10.43g, 0.084 moles), Vazo-64 (AIBN, 0.05 g, 0.0003 moles) and THF (600 ml).The reaction vessel was fitted with a magnetic stirrer, condenser,thermal controller, and a nitrogen inlet. Nitrogen was bubbled throughthe solution for 15 min to remove any dissolved oxygen. The reactionflask was then heated to 60° C. under a passive blanket of nitrogen for20 hrs. The reaction mixture was then added slowly to 6 liters of ethylether with good mechanical stirring. The copolymer precipitated and wascollected by vacuum filtration. The solid was placed in a vacuum oven at30° C. overnight to remove the ether, leaving 21 g of reactive polymer(32% yield). The hydrophilic reactive polymer was placed in a desiccatorfor storage until use.

EXAMPLE 10

This Example illustrates the synthesis of a hydrophilic reactive(linear) copolymer of DMA/GMA, which is used in Examples 13, 14, and 15below, according to the following reaction scheme:

To a 1-liter reaction flask were added distilled N,N-dimethylacrylamide(DMA, 48 g, 0.48 moles), distilled glycidyl methacrylate (GM, 12 g, 0.08moles), Vazo-64 (AIBN, 0.096 g, 0.0006 moles) and toluene (600 ml). Thereaction vessel was fitted with a magnetic stirrer, condenser, thermalcontroller, and a nitrogen inlet. Nitrogen was bubbled through thesolution for 15 min to remove any dissolved oxygen. The reaction flaskwas then heated to 60° C. under a passive blanket of nitrogen for 20hours. The reaction mixture was then added slowly to 6 liters of ethylether with good mechanical stirring. The reactive polymer precipitatedand was collected by vacuum filtration. The solid was placed in a vacuumoven at 30° C. overnight to remove the ether leaving 50.1 g of reactivepolymer (83% yield). The reactive polymer was placed in a desiccator forstorage until use.

EXAMPLE 11

This Example illustrates the synthesis of a water-soluble reactivepolymer of DMA/OFPMA/GMA, according to the following reaction scheme:

To a 500 ml reaction flask were added distilled N,N-dimethylacrylamide(DMA,16 g, 0.16 moles), 1H,1H,5H-octafluoropentylmethacrylate (OFPMA,1g, 0.003 moles, used as received), distilled glycidyl methacrylate (GM,4 g, 0.028 moles) Vazo-64 (AIBN, 0.03 g, 0.00018 moles) and toluene (300ml). The reaction vessel was fitted with a magnetic stirrer, condenser,thermal controller, and a nitrogen inlet. Nitrogen was bubbled throughthe solution for 15 minutes to remove any dissolved oxygen. The reactionflask was then heated to 60° C. under a passive blanket of nitrogen for20 hours. The reaction mixture was then added slowly to 3 liters ofethyl ether with good mechanical stirring. The reactive polymerprecipitated and was collected by vacuum filtration. The solid wasplaced in a vacuum oven at 30° C. overnight to remove the ether leaving19.3 g of reactive polymer (92% yield). The reactive polymer was placedin a desiccator for storage until use.

EXAMPLE 12

This Example illustrates the synthesis of a hydrophilic reactive polymerof DMA/MAA, according to the following reaction scheme:

To a 500 ml reaction flask were added distilled N,N-dimethylacrylamide(DMA, 16 g, 0.16 moles), methacrylic acid (MAA, 4 g, 0.05 moles) Vazo-64(AIBN, 0.033 g, 0.0002 moles) and anhydrous 2-propanol (300 ml). Thereaction vessel was fitted with a magnetic stirrer, condenser, thermalcontroller, and nitrogen inlet. Nitrogen was bubbled through thesolution for 15 minutes to remove any dissolved oxygen. The reactionflask was then heated to 60° C. under a passive blanket of nitrogen for72 hours. The reaction mixture was then added slowly to 3 liters ofethyl ether with good mechanical stirring. The reactive polymerprecipitated and was collected by vacuum filtration. The solid wasplaced in a vacuum oven at 30° C. overnight to remove the ether leaving9.5 g of reactive polymer (48% yield). The reactive polymer was placedin a desiccator for storage until use.

EXAMPLE 13

This Example illustrates the surface treatment of Balafilcon A contactlenses (PureVision® lenses, commercially available from Bausch & Lomb,Inc., Rochester, N.Y.) made from the material of Example 1, whichsurface treatment employed the hydrophilic reactive polymers made fromExample 10 above, according to the following reaction scheme:

A solution of reactive polymer of Example 10 (10.0 g per 1000 ml ofwater) was prepared. Lenses were extracted with three changes of2-propanol over a four-hour period and then with three changes of waterat one-hour intervals. Lenses (36 samples) were then placed in thesolution of reactive polymer. One drop of methyldiethanolamine was addedto catalyze the reaction. The lenses were put through one 30-minuteautoclave cycle.

EXAMPLE 14

This Example illustrates the surface treatment of an RGP Lens Surfaceaccording to the present invention, as shown below. The material wasBoston® XO (hexafocon A) lens, commercially available from Bausch &Lomb, Inc.

A solution of reactive polymer of Example 10 (5.0 g per 100 ml of water)was prepared. Lenses (20 samples) were then placed in the solution ofreactive polymer with two (2) drops of triethanolamine and heated to 55°C. for one (1) hour. The surface-coated lenses were then rinsed offtwice with purified water and allowed to dry. A drop of water placed onan untreated lens would bead up and roll off the surface while a drop ofwater was placed on the treated lens spread completely, wetting the lenssurface.

X-ray Photo Electron Spectroscopy (XPS) data was obtained at the SurfaceScience lab within Bausch and Lomb. A Physical Electronics [PHI] Model5600 XPS was used for the surface characterization. This instrumentutilized a monochromated A1 anode operated a 300 watts, 15 kV and 20milliamps. The base pressure of the instrument was 2.0×10⁻¹⁰ torr andduring operation the pressure was 5.0×10⁻⁸ torr. This instrument madeuse of a hemispherical analyzer. The instrument had an Apolloworkstation with PHI 8503A version 4.0A software. The practical measurefor sampling depth for this instrument at a sampling angle of 45° was 74Å.

Each specimen was analyzed utilizing a low-resolution survey spectra(0-1100 eV) to identify the elements present on the sample surface(10-100Å). Surface elemental compositions were determined fromhigh-resolution spectra obtained on the elements detected in thelow-resolution survey scans. Those elements included oxygen, nitrogen,carbon, silicon and fluorine. Quantification of elemental compositionswas completed by integration of the photoelectron peak areas aftersensitizing those areas with the instrumental transmission function andatomic cross sections for the orbitals of interest. The XPS data for thecoated lenses and controls are given in Table 3 below.

TABLE 3 Sample O N C Si F Lens Posterior Average 22.3 4.8 54.4 10.3 10.9Std dev Lens Anterior Average 19.1 6.7 63.4 2.7 8.1 std dev 0.6 0.3 1.10.6 0.7 Boston ® XO Average 18.7 0.0 56.1 5.2 20.0 (post & ant are thestd dev 0.5 0.0 0.7 0.3 0.4 same) Theoretical Atomic 17 12 71 0 0Concentrations for DMA-co-GMA Reactive Polymer

EXAMPLE 15

This Example illustrates another surface treatment of an Boston® XOcontact lens material, commercially available from Bausch & Lomb, Inc.,according to the following reaction sequence:

A solution of reactive polymers of Example 10 and Example 12 above (2.5g of each polymer per 100 ml of water) was prepared. The mixture ofpolymers was used in an attempt to build a thicker polymer coating via alayering effect. Lenses (20 samples) were then placed in the solution ofreactive polymer with two drops of triethanolamine and heated to 55° C.for one hour. The surface-coated lenses were then rinsed off twice withpurified water and allowed to dry. A drop of water placed on anuntreated lens would bead up and roll off the surface while a drop ofwater placed on the treated lens spread completely wetting the lenssurface. Atomic Force Microscopy (AFM) analysis suggests that thecombination of polymers gave a thicker polymer coating. Comparisonsbetween a Boston® XO lens with no polymer coating (FIG. 1), the polymercoating of Example 14 (FIG. 2), and the coating of this Example 15 (FIG.3) are shown in FIGS. 1 to 3.

X-ray Photo Electron Spectroscopy (XPS) data was obtained at the SurfaceScience lab within Bausch and Lomb. A Physical Electronics [PHI] Model5600 XPS was used for the surface characterization. This instrumentutilized a monochromated A1 anode operated a 300 watts, 15 kV and 20milliamps. The base pressure of the instrument was 2.0×10⁻¹⁰ torr andduring operation the pressure was 5.0×10⁻⁸ torr. This instrument madeuse of a hemispherical analyzer. The instrument had an Apolloworkstation with PHI 8503A version 4.0A software. The practical measurefor sampling depth for this instrument at a sampling angle of 45° was 74Å.

Each specimen was analyzed utilizing a low-resolution survey spectra(0-1100 eV) to identify the elements present on the sample surface(10-100Å). Surface elemental compositions were determined fromhigh-resolution spectra obtained on the elements detected in thelow-resolution survey scans. Those elements included oxygen, nitrogen,carbon, silicon and fluorine. Quantification of elemental compositionswas completed by integration of the photoelectron peak areas aftersensitizing those areas with the instrumental transmission function andatomic cross sections for the orbitals of interest. The XPS data for thecoated lenses and controls are given in Table 4A below.

TABLE 4A Sample O N C Si F Lens Posterior Average 18.8 8.0 67.6 3.7 2.6std dev Lens Anterior Average 18.4 4.2 62.8 4.1 10.5 std dev 0.5 1.2 1.70.4 3.1 Quantumr ® II Control Average 18.7 0.0 56.1 5.2 20.0 (post & antare the std dev 0.5 0.0 0.7 0.3 0.4 same) Theoretical Atomic 17 12 71 00 Concentrations for DMA-co-GMA Reactive Polymer

EXAMPLE 16

This Example illustrates the surface treatment of Balafilcon A contactlenses (PureVision® lenses, commercially available from Bausch & Lomb,Inc., Rochester, N.Y.) made from the material of Example 1, whichsurface treatment employed the hydrophilic reactive polymers made fromExample 11 above, according to the following reaction scheme:

Two solutions of the reactive polymer of Example 11 were prepared (seeTable 4B below). Lenses were extracted in 2-propanol for 4 hours andthen placed in purified water for 10 minutes. The water bath was thenchanged, and the lenses were allowed to soak for an additional 10minutes. Lenses (30 samples) were then placed in each solution ofreactive polymer with one drop of methyldiethanolamine to catalyze thereaction. The lenses were put through one 30-minute autoclave cycle. Thesolution in the vials was then replaced with purified water twice, andthe samples were again autoclaved. This procedure was used to remove anyhydrophilic polymer not chemically bonded to the lens.

TABLE 4B Sample Polymer Concentration No. Lenses treated A 1.0% (2.5g/250 ml H₂O) 30 B 2.0% (5 g/250 ml H₂O) 30 Control None 30

The atomic force microscopy (AFM) images of the control is shown in FIG.4. FIG. 5 and FIG. 6 show the surface of Samples A and B, respectively.The hydrophilic coating is clearly shown in FIGS. 5 and 6 compared tothe surface image of the Control Sample. Elemental analysis by XPS alsoindicates that the material surface has been modified. The XPS data wasobtained at the Surface Science lab within Bausch and Lomb. A PhysicalElectronics [PHI] Model 5600 XPS was used for the surfacecharacterization. This instrument utilized a monochromated Al anodeoperated a 300 watts, 15 kV and 20 milliamps. The base pressure of theinstrument was 2.0×10⁻¹⁰ torr and during operation the pressure was5.0×10⁻⁸ torr. This instrument made use of a hemispherical analyzer. Theinstrument had an Apollo workstation with PHI 8503A version 4.0Asoftware. The practical measure for sampling depth for this instrumentat a sampling angle of 45° was 74 Å.

Each specimen was analyzed utilizing a low-resolution survey spectra(0-1100 eV) to identify the elements present on the sample surface(10-100Å). Surface elemental compositions were determined fromhigh-resolution spectra obtained on the elements detected in thelow-resolution survey scans. Those elements included oxygen, nitrogen,carbon, silicon and fluorine. Quantification of elemental compositionswas completed by integration of the photoelectron peak areas aftersensitizing those areas with the instrumental transmission function andatomic cross sections for the orbitals of interest. The XPS data isgiven in Table 4C below.

TABLE 4C Sample O1s N1s C1s Si2p F1s Control Posterior Average 17.7 7.266.9 8.1 0.0 std dev 0.9 0.2 0.8 0.3 0.0 Control Anterior Average 17.97.0 66.9 8.2 0.0 std dev 0.6 0.6 0.7 0.4 0.0 A Posterior Average 17.98.9 69.5 1.8 2.0 std dev 0.3 0.2 0.6 0.6 0.2 A Anterior Average 17.7 9.169.7 1.7 1.9 std dev 0.3 0.3 0.8 0.3 0.2 B Posterior Average 18.0 8.969.9 1.2 2.1 std dev 0.3 0.5 1.0 0.1 0.4 B Anterior Average 17.8 8.870.0 1.3 2.0 std dev 0.2 0.3 0.6 0.3 0.0 Theoretical Atomic Conc. 17.111.0 70.1 0.0 1.8 DMA-co-OFPMA-co-GMA From Example 11

EXAMPLE 17

This Example illustrates improved inhibition of lipid deposition for theBalafilcon A lenses (PureVision® lenses) coated by reaction with varioushydrophilic reactive polymers according to the present invention. SampleE lenses was coated using a 1% solution of the DMA/OFPMA/GM copolymer ofExample 11, and Sample EE lenses was coating using a 2% solution of thesame polymer. Samples F and FF lenses were respectfully coated using 1%and 2% solutions of the DMA/GM copolymer of Example 10. The lenses wereplaced in an aqueous solution of the reactive hydrophilic polymer with acatalyst and run through one autoclave cycle. The lenses were thenrinsed in HPLC grade water, placed in fresh HPLC water, and autoclavedfor a second time. The control lenses (no surface treatment) were placedin HPLC water and autoclaved. One control lens was the Balafilicon Alens prior to any surface treatment. A second control lens was thecommercial PureVisiono lens with a oxidative plasma surface treatment.For the lipid analysis, Gas Chromatography (GC) was employed, includingan HP Ultra 1 column with an FID detector and He carrier gas. In the invitro lipid deposition protocol, six lenses were subject to depositionfor each of the lens types tested, employing a lipid mix of palmiticacid methyl ester, cholesterol, squalene and mucin in MOPS buffer. Mucinwas utilized as a surfactant to aid in the solubilization of the lipids.The above lipid mix in the amount of 1.5 ml was added to the testlenses, which were subject to deposition in a 37° C. shaking-water bathfor 24 hours. The lenses were then removed from the water bath, rinsedwith ReNu® Saline to remove any residual deposition solution, and placedin glass vials for extraction. A three hour 1:1 CHC1₃/MeOH extractionwas subsequently followed by a three hour hexane extraction. Extractswere then combined and run on the GC chromatograph. Standard solutionsof each of the lipids in the deposition mix were made in 1:1 CHC1₃/MeOHand run on the GC for determination of the concentration of lipidextracted from the lenses. The in vitro lipid deposition profiles forthe lenses tested, using the protocol above, are shown in Table 5 below.

TABLE 5 Average Lipid Sample Concentration* (μg) E 39.9 EE 36.7 F 51.2FF 39.6 Plasma-Oxidation 117 Control No-Surface-Treatment 243.3 Controllenses *The average represents the deposition profile for 6 depositedlenses.

The results indicate that lenses coated according to the presentinvention can exhibit reduced lipid deposition, a particularlyadvantageous property for continuous-wear hydrogel lenses.

EXAMPLE 18 Procedure

A solution was prepared, of reactive polymer,N,N-dimethylacrylamide-co-glycidyl methacrylate (0.4 g/20 ml of HPLCwater) and eight drops of triethanolamine. Polished buttons (4 samples)were imaged by non-contact atomic force microscopy then cleaned byrubbing with HPLC grade water. The substrates were then placed in the4-5 ml of reactive polymer solution, in sealed lens flat packs andheated to 55° C. for one hour. The treated polymer buttons were thenrinsed off twice with HPLC water and allowed to dry. A drop of waterplaced on an untreated lens would bead up and roll off the surface whilea drop of water was placed on the treated lens spread completely wettingthe lens surface.

The buttons were then cleaned with 3-4 drops of Bostono Advance brandcontact lens cleaner, a sterile surfactant solution containing silicagel as an abrasive-cleaning agent, followed by rinsing (2 times with)HPLC grade water. The polymer buttons were allowed to dry and AFM imageswere again recorded. The images appeared to be equivalent to those takenbefore any coating was applied.

The coating procedure outlined above was repeated and AFM images wererecorded. The material again appeared to be coated with polymer.

The procedure of this Example 18 was repeated with three fresh RGPcontact lens material buttons. Surface analysis for the repeatedexperiment was x-ray photoelectron spectroscopy (XPS). The XPS data isgiven in the table below. It is clearly evident from the data givenbelow, looking at the increase of nitrogen (N, from the coating polymer)and the corresponding decreases of silicon (Si) and fluorine (F) in thesubstrate, that the polymer coating was applied, removed and appliedagain.

TABLE 6 XPS Results for Example 18 Sample O N C Si F Button BeforeCoating 17.9 0.0 57.9 5.7 18.5 button 1 18.2 0.0 54.8 5.3 20.7 18.9 0.052.7 5.3 23.0 button 2 17.5 0.0 55.1 6.0 21.5 button 3 18.9 0.0 54.0 6.220.9 button 4 18.1 0.0 54.3 5.9 21.7 Average 18.3 0.0 54.8 5.7 21.0Standard Deviation 0.6 0.0 1.7 0.4 1.5 Coated Button 19.8 4.9 66.7 2.85.8 button 1 19.7 6.0 66.3 2.5 5.6 20.3 6.3 66.1 2.6 4.8 button 2 20.55.2 65.1 2.8 6.4 button 3 18.6 3.3 76.1 1.3 0.8 button 4 16.8 4.3 78.90.0 0.0 Average 19.3 5.0 69.8 2.0 3.9 Standard Deviation 1.4 1.1 6.0 1.12.8 Button After Removal 20.4 0.0 59.3 4.7 15.6 button 1 of Coating 21.30.0 60.4 5.0 13.4 18.3 0.0 58.6 5.7 17.5 button 2 18.5 0.0 56.2 6.1 19.2button 3 19.5 0.0 56.6 6.5 17.4 button 4 18.6 0.0 57.9 5.8 17.7 Average19.4 0.0 58.2 5.6 16.8 Standard Deviation 1.2 0.0 1.6 0.7 2.0 ButtonAfter Re-coating 20.6 3.2 74.1 1.4 0.7 button 1 20.6 3.7 74.2 0.9 0.524.6 5.1 67.1 1.9 1.4 button 2 19.9 5.6 69.0 2.5 3.0 button 3 21.1 3.373.3 1.2 1.1 button 4 20.5 4.9 65.5 3.6 5.5 Average 21.2 4.3 70.5 1.92.0 Standard Deviation 1.7 1.0 3.8 1.0 1.9

FIG. 7 is an AFM topographical image (50 μm²) of an RGP contact lensmaterial button of Example 18 prior to surface treatment.

FIG. 8 is an AFM topographical image (50 μm²) of the surface of an RGPbutton after a first hydrophilic polymer coating step in Example 18.

FIG. 9 is an AFM topographical image (50 μm²) of the surface of an RGPbutton after abrasive removal of the polymer coating in Example 18.

FIG. 10 is an AFM topographical image (50 μm²) of the surface of an RGPbutton after the hydrophilic polymeric surface was re-applied in Example18.

EXAMPLE 19

This Example illustrates the synthesis of the monomer12-methacryloyloxydodecanoic acid useful in the synthesis of reactivepolymers. A reference can be found in the U.S. Pat. No. 4,485,045 byRegen entitled “Sythetic Phosphatidyl Cholines Useful in FormingLiposomes”.

To a 2 liter reaction flask were added 12-hydroxydodecanoic acid (99.5g, 0.46 moles), anhydrous pryidine (56 ml) and anhydrous tetrahydrofuran(1,000 ml). The mixture was cooled in an ice bath to 0° C. A solution ofdistilled methacryloyl chloride (48 g, 0.046 moles) in anhydroustetrahydrofuran (200 ml) was slowly added to the cold reaction mixturewith good stirring. Following the addition the mixture was allowed toreach room temperature and left stirring overnight. The solvent wasremoved by flash evaporation and the residue was taken up in 1 liter ofethyl ether. The ether solution was washed with purified water, driedover magnesium sulfate and again flash evaporated leaving 98.5 grams ofcrude product. The crude product was further purified by silica gelchromatography using a 1:2 mixture of ethylacetate and heptane to give a63% yield.

EXAMPLE 20

Example 20 illustrates the synthesis of a hydrophilic reactive polymerof N,N-dimethylacrylamide-co-12-methacryloyloxydodecanoic acid.

To a 500 ml reaction flask were added distilled N,N-dimethylacrylamide(DMA, 15.2 g, 0.153 moles), 12-methacryloxydodecanoic acid (LMAA, 4.8 g,0.017 moles) Vazo 64 (AIBN, 0.032 g, 0.0002 moles) and anhydroustetrahydrofuran (200 ml). The reaction vessel was fitted with a magneticstirrer, condenser, thermal controller and a nitrogen inlet. Nitrogenwas bubbled through the solution for 15 minutes to remove any dissolvedoxygen. The reaction flask was then heated to 60° C. under a passiveblanket of nitrogen for 72 hours. The reaction mixture was then addedslowly to 2.5 L of heptane with good mechanical stirring. The reactivepolymer precipitated and was collected by vacuum filtration. The solidwas placed in a vacuum oven at 30° C. overnight to remove the etherleaving 15 g of reactive polymer (75% yield). The reactive polymer wasplaced in a desiccator for storage until use.

EXAMPLE 21

This Example illustrates the synthesis of a hydrophilic reactive polymerof N,N-dimethylacrylamide-co-octafluoropentylmethacrylate-co-12-methacryloyloxydodecanoic acid.

To a 500 ml reaction flask were added distilled N,N-dimethylacrylamide(DMA, 15 g, 0.151 moles), 1H,1H,5H-octafluoropentylmethacrylate (OFPMA0.5 g, 0.0016 moles, used as received), 12-methacryloxydodecanoic acid(LMAA, 4.5 g, 0.0158 moles) Vazo 64 (AIBN, 0.032 g, 0.0002 moles) andanhydrous tetrahydrofuran (200 ml). The reaction vessel was fitted witha magnetic stirrer, condenser, thermal controller and a nitrogen inlet.Nitrogen was bubbled through the solution for 15 minutes to remove anydissolved oxygen. The reaction flask was then heated to 60° C. under apassive blanket of nitrogen for 72 hours. The reaction mixture was thenadded slowly to 2.5 L of heptane with good mechanical stirring. Thereactive polymer precipitated and was collected by vacuum filtration.The solid was placed in a vacuum oven at 30° C. overnight to remove theether leaving 18.7 g of reactive polymer (94% yield). The reactivepolymer was placed in a desiccator for storage until use.

EXAMPLE 22

Example 22 illustrates the synthesis of a hydrophilic reactive polymerof N,N-dimethylacrylamide-co-laurylmethacrylate-co-glycidylmethacrylate.

To a 1000 ml reaction flask were added distilled N,N-dimethylacrylamide(DMA,32 g, 0.32 moles), laurylmethacyy;ate (LMA, 1.5 g, 0.006 moles,used as received), distilled glycidyl methacrylate (GM, 8 g, 0.056moles) Vazo-64 (AIBN, 0.06 g, 0.00036 moles) and tetrahydrofuran (600ml). The reaction vessel was fitted with a magnetic stirrer, condenser,thermal controller and a nitrogen inlet. Nitrogen was bubbled throughthe solution for 15 minutes to remove any dissolved oxygen. The reactionflask was then heated to 60° C. under a passive blanket of nitrogen for20 hours. The reaction mixture was then added slowly to 3 L of ethylether with good mechanical stirring. The reactive polymer precipitatedand was collected by vacuum filtration. The solid was placed in a vacuumoven at 30° C. overnight to remove the ether leaving 29.2 g of reactivepolymer (70% yield). The reactive polymer was placed in a desiccator forstorage until use.

Many other modifications and variations of the present invention arepossible in light of the teachings herein. It is therefore understoodthat, within the scope of the claims, the present invention can bepracticed other than as herein specifically described.

What is claimed is:
 1. A method for treating the surface of a medicaldevice comprising: (a) forming a medical device from a materialcomprising monomeric units having reactive functionalities selected fromthe group consisting of azlactone, carboxylic acid, amine, hydroxy andepoxy functionalities, and combinations thereof; (b) forming ahydrophilic reactive polymer having complementary reactivefunctionalities along the polymer chain, said complementary reactivefunctionalities selected from the group consisting of azlactone,isocyanate, acid anhydride, epoxy, hydroxy, primary amine, secondaryamine and carboxylic acid functionalities, and combinations thereof,wherein: when the hydrophilic reactive polymer comprises hydroxy oramine complementary reactive functionalities, the medical devicemonomeric units comprise azlactone reactive functionalities, or when thehydrophilic reactive polymer comprises carboxylic acid complementaryfunctionality, the medical device monomeric units comprise epoxyreactive functionalities; (c) reacting the hydrophilic reactive polymerof (b) having complementary reactive functionalities along the polymerchain with said medical device monomeric unit reactive functionalitieson or near the surface of the medical device of (a), thus forming abiocompatible surface on the medical device; (d) removing thebiocompatible surface of step (c); and (e) repeating steps (b) and (c)to form a renewed biocompatible surface on said medical device havingproperties similar to the original biocompatible surface of step (c). 2.The method of claim 1, wherein the medical device is a silicone contactlens or intraocular lens and the hydrophilic reactive polymer isuncolored.
 3. The method of claim 1, wherein the medical device is asilicone hydrogel, continuous-wear contact lens.
 4. The method of claim3 wherein said removing step (d) further comprises abrading saidbiocompatible surface with an abrasive particulate in an aqueous carriersolution.
 5. The method of claim 4, wherein said abrasive particulatecomprises silica or alumina.
 6. The method of claim 1, wherein thehydrophilic reactive polymer comprises 1 to 100 mole percent ofmonomeric units having said reactive functionalities.
 7. The method ofclaim 1, wherein the hydrophilic reactive polymer comprises 0 to 99 molepercent of monomeric units that are derived from non-reactivehydrophilic monomers.
 8. The method of claim 1, wherein the polymercomprises 50 to 95 mole percent of monomeric units derived fromnon-reactive hydrophilic monomers selected from the group consisting ofacrylamides, lactones, poly(alkylenepoxy)methacrylates, methacrylic acidor hydroxyalkyl methacrylates and 5 to 50 percent of monomeric unitsderived from functionally reactive monomers selected from the groupconsisting of epoxy, azlactone, and anhydride containing monomers. 9.The method of claim 1, wherein the medical device comprises a siliconehydrogel that is a polymerization product of a mixture comprising asilicon-containing monomer and a hydrophilic monomer.
 10. The method ofclaim 1, wherein the hydrophilic reactive polymer comprises 0 to 35 molepercent monomeric units derived from hydrophobic monomers.
 11. Themethod of claim 1, wherein the hydrophilic polymer comprises oxazolinonemoieties having the following formula:

wherein R³ and R⁴ independently can be an alkyl group having 1 to 14carbon atoms; a cycloalkyl group having 3 to 14 carbon atoms; an arylgroup having 5 to 12 ring atoms; an arenyl group having 6 to 26 carbonatoms; and 0 to 3 heteroatoms selected from S, N, and nonperoxidic 0; orR³ and R⁴ taken together with the carbon to which they are joined canform a carbocyclic ring containing 4 to 12 ring atoms, and n is aninteger 0 or
 1. 12. The method of claim 11, wherein the polymercomprises the reaction product of a mixture of monomers comprising themonomer represented by the general formula:

where R¹ and R² independently denote a hydrogen atom or a lower alkylradical with one to six carbon atoms, and R³ and R⁴ independently denotealkyl radicals with one to six carbon atoms or a cycloalkyl radicalswith 5 or 6 carbon atoms.
 13. The method of claim 12, wherein themonomer is selected from the group consisting of2-isopropenyl-4,4-dimethyl-2-oxazolin-5-one and2-vinyl-4,4-dimethyl-2-oxazolin-5-one.
 14. The method of claim 11, inthe medical device is dipped in a solution comprising at least onehydrophilic reactive polymer in the absence of a coloring substance. 15.The method of claim 1 wherein said removing step (d) further comprisesabrading said biocompatible surface.
 16. The method of claim 1, whereinthe medical device is a rigid contact lens.
 17. The method of claim 16,wherein the rigid contact lens is a rigid-gas-permeable contact lens.